By Tim Parsons
School of Public Health

Scientists have identified a new compound called CDDO-Im that protects against the development of liver cancer in laboratory animals. Experiments led by researchers at the Johns Hopkins Bloomberg School of Public Health show CDDO-Im to be effective at doses 100 times lower than other compounds known to prevent cancer in people. Because of its makeup, the researchers believe CDDO-Im could be particularly effective in preventing cancers with a strong link to inflammation, such as liver, colon, prostate and gastric cancers. It could also play a role in preventing diseases such as neurodegeneration, asthma and emphysema. The findings are featured in the Feb. 15 issue of the journal Cancer Research.

CDDO-Im is a synthetic compound that belongs to a class of cancer-fighting compounds called triterpenoids under development by Michael Sporn and other study co-authors at Dartmouth Medical School. It is derived from oleanolic acid, a naturally occurring substance found in many plants. Other oleanolic derivatives are known to reduce tumor growth in animals and humans.

Researchers believe CDDO-Im works by activating Nrf2, a master switch known to direct certain enzymes to stimulate the cell's defense mechanisms and remove harmful chemicals from cells. "Activation of the Nrf2 pathway with CDDO-Im could provide protection against a number of diseases triggered by environmental agents," said lead author Thomas Kensler, a professor with the Bloomberg School's Department of Environmental Health Sciences.

In their research, Kensler and his colleagues treated laboratory rats with varying doses of CDDO-Im. Two days later, the rats were given aflatoxin, a naturally occurring cancer-causing toxin. CDDO-Im treatment led to an 85 percent reduction in precancerous lesions at the lowest dose of 50 micrograms per rat and a 99 percent reduction at the highest dose of 5 milligrams.

Like other compounds derived from oleanolic acid, CDDO-Im has strong anti-inflammatory properties, which the researchers say makes it ideally suited to the prevention of certain cancers. "When cells become inflamed, they can produce reactive molecules, called free radicals, that can damage DNA and promote cancer development," Kensler said. "CDDO-Im can also inhibit cancer formation by interfering with this inflammatory process."

Because it can stimulate the body's defense mechanisms at such low doses, Kensler believes that CDDO-Im is an excellent candidate for cancer prevention in humans. "If this compound can produce such a potent and dramatic reduction in the number of precancerous growths, it should have an equally dramatic impact on the development of actual cancers. This study suggests that we may be on the right track in terms of chemoprevention. It may open the door for a new class of compounds that could prevent a number of diseases," Kensler said.

The National Institute of Environmental Health Sciences and the National Cancer Institute, agencies of the National Institutes of Health, provided funding to researchers at the Bloomberg School for the study. Authors are Melinda S. Yates, Mi-Kyoung Kwak, Patricia A. Egner, John D. Groopman, Sridevi Bodreddigari, Thomas R. Sutter, Karen J. Baumgartner, Bill D. Roebuck, Karen T. Liby, Mark M. Yore, Tasdashi Honda, Gordon W. Gribble, Sporn and Kensler.

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